Efficacy of late concurrent hypo-fractionated radiotherapy in advanced melanoma patients failing anti-PD-1 monotherapy.
晚期同步低分割放疗对单药治疗失败的晚期黑色素瘤患者 anti-PD-1 疗效。
- 作者列表："Funck-Brentano E","Baghad B","Fort M","Aouidad I","Roger A","Beauchet A","Otmezguine Y","Blom A","Longvert C","Boru B","Saiag P
:Advanced melanoma patients who failed anti-PD-1 therapy have limited options. We analyzed a cohort of 133 advanced melanoma patients receiving anti-PD-1 monotherapy in a referral center between April 2015 and December 2017 and included the 26 patients with confirmed progressive (PD) or stable disease who received additional radiotherapy with an unmodified anti-PD-1 mAb regimen. Tumor evaluations were done on radiated and non-radiated (RECIST1.1) lesions, with abscopal effect defined as a partial (PR) or complete response (CR) outside radiated fields. Primary endpoint was the CR + PR rate in radiated + non-radiated lesions. Secondary endpoints were progression-free survival (PFS), melanoma-specific survival (MSS), and safety. First late radiotherapy, consisting of hypo-fractionated radiotherapy (3-5 sessions, 20-26 Gy), standard palliative radiotherapy, or brain radiosurgery was begun after a median of 6.3 months of anti-PD-1 in 23, 2, and 1 patient(s), respectively. Best response was 8 (31%) CR, 2 (8%) profound PR allowing surgical resection of remaining metastases, and 16 (62%) PD. Abscopal effect was seen in 35% of patients. Median PFS and MSS since anti-PD-1 initiation was 15.2 [95%CI: 8.0-not achieved (na)] and 35.3 [95%CI: 18.5-na] months, respectively. PFS curves seemed to achieve a plateau. We discontinued anti-PD-1 therapy in 9/10 of patients with no residual evaluable disease and observed one relapse after a median of 10 months off anti-PD1-therapy. No unusual adverse event was recorded. Limitations of the study include its retrospective nature and limited size. Hypo-fractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in patients who previously failed anti-PD-1 therapy. Controlled studies are needed. This article is protected by copyright. All rights reserved.
: Anti-PD-1 治疗失败的晚期黑色素瘤患者的选择有限。我们分析了 2015年4月至 2017年12月在转诊中心接受 anti-PD-1 单药治疗的 133 例晚期黑色素瘤患者的队列，包括 26 例确诊为进展 (PD) 的患者。或病情稳定者，接受未改良 anti-PD-1 mAb 方案的额外放疗。对辐射和非辐射 (RECIST1.1) 病灶进行肿瘤评价，局部效应定义为辐射野外的部分 (PR) 或完全反应 (CR)。主要终点是辐射 + 非辐射病变中的 cr + pr 率。次要终点是无进展生存期 (PFS) 、黑色素瘤特异性生存期 (MSS) 和安全性。首次晚期放疗，包括低分割放疗 (3-5 次，20-26 gy) 、标准姑息放疗、在分别有 23 例、 2 例和 1 例患者的 anti-PD-1 中位数为 6.3 个月后，开始或脑放射手术。最佳反应为 8 例 (31%) CR，2 例 (8%) 深 PR 允许手术切除剩余转移灶，16 例 (62%) PD。35% 的患者可见局部反应。Anti-PD-1 开始后的中位 PFS 和 MSS 分别为 15.2 [95% CI: 8.0-未达到 (na)] 和 35.3 [95% CI: 18.5-na] 个月。PFS 曲线似乎达到平台期。我们在 9/10 没有残留疾病的患者中停止了 anti-PD-1 治疗，并观察到中位治疗后 10 个月复发 anti-PD1-therapy。未记录到异常不良事件。该研究的局限性包括其回顾性性质和规模有限。低分割放疗可能会提高 anti-PD1 治疗失败患者的 anti-PD-1 疗效。需要对照研究。本文受版权保护。保留所有权利。
METHODS::In colorectal cancer (CRC), hepatic arterial infusion (HAI) chemotherapy may convert primarily unresectable CRC liver metastases (CLM) into resectability, although the risk of metastatic recurrence remains high after CLM ablation. We investigated the role of antitumour immunity invoked by first-line oxaliplatin-HAI for long-term CLM outcome. In a prospective study cohort of primarily unresectable CLM, we assessed patients' fms-related tyrosine kinase 3 ligand (FLT3LG) in serum, reflecting opportune intratumoural immune activity, at baseline and following 1-3 sequences of oxaliplatin-HAI. The end points were CLM resectability and overall survival. Patients who presented an immediate twofold increment of circulating FLT3LG during the treatment and at its completion were scored as CLM resectable (16.4% with both features), were alive at final follow-up 8-12 years later. All patients experienced FLT3LG increase during the treatment course, but those who remained unresectable or had the disease converted but presented a slow and gradual FLT3LG accretion, later died of the metastatic disease. These data provide further support to our previous findings that tumour-directed immunity invoked by oxaliplatin-containing therapy predicts excellent outcome of early advanced CRC if macroscopic tumour ablation is rendered possible by the 'classic' tumour response to the cytotoxic treatment.
METHODS::Prostate cancer is one of the primary causes of death around the world. As an important drug, flutamide has been used in the clinical diagnosis of prostate cancer. However, the over dosage and improper discharge of flutamide could affect the living organism. Thus, it necessary to develop the sensor for detection of flutamide with highly sensitivity. In this paper, we report the synthesis of lanthanum cobaltite decorated halloysite nanotube (LCO/HNT) nanocomposite prepared by a facile method and evaluated for selective reduction of flutamide. The as-prepared LCO/HNT nanocomposite shows the best catalytic performance towards detection of flutamide, when compared to other bare and modified electrodes. The good electrochemical performance of the LCO/HNT nanocomposite modified electrode is ascribed to abundant active sites, large specific surface area and their synergetic effects. Furthermore, the LCO/HNT modified electrode exhibits low detection limit (0.002 μM), wide working range (0.009-145 μM) and excellent selectivity with remarkable stability. Meaningfully, the developed electrochemical sensor was applied in real environmental samples with an acceptable recovery range.
METHODS::Several studies have indicated that cancer-associated fibroblasts (CAFs) could promote cancer progression in many malignancies. However, the mechanism by which CAFs promote the growth and metastasis of lung cancer remains poorly defined. In the present study, CAFs and normal fibroblasts (NFs) were isolated from human lung cancer and adjacent tissue. The data showed that the conditional medium (CM) of CAFs could increase the proliferation, migration and invasion of lung cancer cells. Vascular cell adhesion molecule-1 (VCAM-1) showed a higher expression in CAF-CM than NF-CM, and blocking VCAM-1 in CAF-CM attenuated the proliferation and invasion of cancer cells. Further, the results showed that VCAM-1 secreted from CAFs activated AKT and MAPK signaling via receptor α4β1 integrin (very-late antigen (VLA)-4) in lung cancer cells. Moreover, CAFs promoted VCAM-1 expression and tumor growth in vivo. Additionally, bioinformatics analysis indicated a positive correlation on the CAF marker protein alpha-smooth muscle actin (α-SMA) and VCAM-1 expression, which was associated with a poor prognosis in lung cancer patients. These findings demonstrate that the VCAM-1 secreted from CAFs enhances growth and invasion by activating the AKT and MAPK signaling of lung cancer cells.